Exome Survey and Candidate Gene Re-Sequencing Identifies Novel Exstrophy Candidate Genes and Implicates in Disease Formation.

Background: The bladder exstrophy-epispadias complex (BEEC) is a spectrum of congenital abnormalities that involves the abdominal wall, the bony pelvis, the urinary tract, the external genitalia, and, in severe cases, the gastrointestinal tract as well.

Methods: Herein, we performed an exome analysis of case-parent trios with cloacal exstrophy (CE), the most severe form of the BEEC. Furthermore, we surveyed the exome of a sib-pair presenting with classic bladder exstrophy (CBE) and epispadias (E) only.

A genome-wide association study with tissue transcriptomics identifies genetic drivers for classic bladder exstrophy.

Classic bladder exstrophy represents the most severe end of all human congenital anomalies of the kidney and urinary tract and is associated with bladder cancer susceptibility. Previous genetic studies identified one locus to be involved in classic bladder exstrophy, but were limited to a restrict number of cohort. Here we show the largest classic bladder exstrophy genome-wide association analysis to date where we identify eight genome-wide significant loci, seven of which are novel.

First genome-wide association study of esophageal atresia identifies three genetic risk loci at , //, and .

Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is the most common congenital malformation of the upper digestive tract. This study represents the first genome-wide association study (GWAS) to identify risk loci for EA/TEF. We used a European case-control sample comprising 764 EA/TEF patients and 5,778 controls and observed genome-wide significant associations at three loci.

A Prevalence Estimation of Exstrophy and Epispadias in Germany From Public Health Insurance Data.

The prevalence of rare diseases is very important for health care research. According to the European Surveillance of Congenital Anomalies (EUROCAT) registers, the live prevalence for exstrophy and/or epispadias (grades 1-3) is reported with 1:23,255 (95% CI: 1:26,316; 1:20,000). A Europe-wide prevalence evaluation based on reports from excellence centers estimates a prevalence for exstrophies of 1:32,200 and for isolated epispadias of 1:96,800 in 2010.

Parental risk factors for congenital diaphragmatic hernia - a large German case-control study.

Background: Evidence for periconceptional or prenatal environmental risk factors for the development of congenital diaphragmatic hernia (CDH) is still scarce. Here, in a case-control study we investigated potential environmental risk factors in 199 CDH patients compared to 597 healthy control newborns.

Methods: The following data was collected: time of conception and birth, maternal BMI, parental risk factors such as smoking, alcohol or drug intake, use of hairspray, contact to animals and parental chronic diseases.

Treatment Strategies and Outcome of the Exstrophy-Epispadias Complex in Germany: Data From the German CURE-Net.

To evaluate the impact of reconstructive strategies and post-operative management on short- and long-term surgical outcome and complications of classical bladder exstrophy (CBE) patients' comprehensive data of the multicenter German-wide Network for Congenital Uro-Rectal malformations (CURE-Net) were analyzed. Descriptive analyses were performed between 34 prospectively collected CBE patients born since 2009, median 3 months old [interquartile range (IQR), 2-4 months], and 113 cross-sectional patients, median 12 years old (IQR, 6-21 years). The majority of included individuals were males (67%).

Human exome and mouse embryonic expression data implicate ZFHX3, TRPS1, and CHD7 in human esophageal atresia.

Introduction: Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) occurs approximately 1 in 3.500 live births representing the most common malformation of the upper digestive tract. Only half a century ago, EA/TEF was fatal among affected newborns suggesting that the steady birth prevalence might in parts be due to mutational de novo events in genes involved in foregut development.

Exome chip association study excluded the involvement of rare coding variants with large effect sizes in the etiology of anorectal malformations.

Introduction: Anorectal malformations (ARM) are rare congenital malformations, resulting from disturbed hindgut development. A genetic etiology has been suggested, but evidence for the involvement of specific genes is scarce. We evaluated the contribution of rare and low-frequency coding variants in ARM etiology, assuming a multifactorial model.

Needs Assessment in Care of Adults With Anorectal Malformations and Exstrophy-Epispadias Complex in Germany.

Medical needs of adults with anorectal malformations (ARM) and the exstrophy-epispadias complex (EEC) are not fully understood. Therefore, the aim of the study was to evaluate how affected individuals get along with the current national medical care and what their medical or social long-term requirements are. Between 11/2014-07/2016 all adult members (≥18 years, ARM = 113, EEC = 126) of the German self-help organizations SoMA e.

Utilization and determinants of follow-up colonoscopies within 6 years after screening colonoscopy: Prospective cohort study.

Previous studies have reported that repeat colonoscopies were often not conducted in the recommended time interval after screening colonoscopy. We prospectively followed participants of screening colonoscopy from Germany for 6 years to investigate utilization and determinants of repeat colonoscopies. In a longitudinal study on the effectiveness of screening colonoscopy in the state of Saarland (Germany), participants who had a screening colonoscopy between 2005 and 2007 were contacted by mail 6 years after screening and requested to fill in a standardized questionnaire on utilization of repeat colonoscopies.

Association Between Exstrophy-epispadias Complex And Congenital Anomalies: A German Multicenter Study.

Objective: To further investigate associated anomalies in exstrophy-epispadias complex (EEC) patients congenital uro-rectal malformations network (CURE-Net) database was systematically screened. In literature the EEC comprises a spectrum of anomalies, mainly occurring "isolated" without additional congenital defects. Nevertheless, previous epidemiological studies indicated a higher association with renal, anorectal, and lower neurotubular anomalies, which may originate from the same developmental morphogenetic fields.

Maternal drug use and the risk of anorectal malformations: systematic review and meta-analysis.

Background: Origin of anorectal malformations (ARM) are considered multifactorial. Several genetic and non-genetic risk factors are discussed in literature. Maternal periconceptional medical drug use as possible risk factor, however, has not been reviewed systematically.

Epidemiologic analysis of families with isolated anorectal malformations suggests high prevalence of autosomal dominant inheritance.

Background: Anorectal malformations (ARM) are rare abnormalities that occur in approximately 1 in 3000 live births with around 40% of patients presenting with isolated forms. Multiple familial cases reported, suggest underlying genetic factors that remain largely unknown. The recurrence in relatives is considered rare, however transmission rates of ARM by affected parents have never been determined before.

Sexual Function and Quality of Life in Adult Male Individuals with Exstrophy-Epispadias Complex-a Survey of the German CURE-Network.

Objective: To investigate sexual function and quality of life (QoL) in adult male individuals with exstrophy-epispadias complex (EEC). Data from the German Network for Congenital Urorectal Malformations (CURE-Net) were used.

Patients And Methods: Fifty-one male participants (≥18 years) recruited by CURE-Net between 2009 and 2012 were re-contacted per mail and asked to fill out 4 questionnaires including International Index of Erectile Function (IIEF-5), Cologne Assessment of Erectile Dysfunction (KEED), the Short-Form 36 (SF-36), and one self-designed questionnaire about their medical history, current health status, and sexual experience.

Array-based molecular karyotyping in 115 VATER/VACTERL and VATER/VACTERL-like patients identifies disease-causing copy number variations.

Background: The acronym VATER/VACTERL refers to the rare nonrandom association of the following component features (CF): vertebral defects (V), anorectal malformations (A), cardiac defects (C), tracheoesophageal fistula with or without esophageal atresia, renal malformations (R), and limb defects (L). Patients presenting with at least three CFs are diagnosed as having VATER/VACTERL association while patients presenting with only two CFs are diagnosed as having VATER/VACTERL-like phenotypes. Recently, rare causative copy number variations (CNVs) have been identified in patients with VATER/VACTERL association and VATER/VACTERL-like phenotypes.

Complication Rates in Colonoscopy Screening for Cancer.

Background: Screening colonoscopy has been offered in Germany since 2002. Complications during colonoscopy were reported to be rare, but data on potential complications after colonoscopy are sparse. We aimed to comprehensively assess the frequency of complications arising during or within four weeks of screening colonoscopy.

Should Screening Colonoscopy Be Offered From Age 50?

Background: The introduction of colonoscopic screening in 2002 for persons aged 55 and older was followed by a marked decline in the incidence of colon cancer in the corresponding age groups in Germany. The prevalence of colorectal neoplasia among persons aged 50 to 54 has remained unknown until now. Expert committees currently recommend colonoscopic screening for persons aged 50 and older.

Screening for Bowel Cancer: Increasing Participation via Personal Invitation.

Background: Participation rates in bowel cancer screening programs in Germany continue to be low. In a model project, a logistically simple procedure for inviting patients to participate was tested as a means of increasing participation.

Methods: A randomized trial was performed involving persons residing in the German federal state of Saarland who had either their 50th or their 55th birthday in the year beginning on 1 April 2012 (18 560 and 16 824 persons, respectively).

ISL1 is a major susceptibility gene for classic bladder exstrophy and a regulator of urinary tract development.

Previously genome-wide association methods in patients with classic bladder exstrophy (CBE) found association with ISL1, a master control gene expressed in pericloacal mesenchyme. This study sought to further explore the genetics in a larger set of patients following-up on the most promising genomic regions previously reported. Genotypes of 12 markers obtained from 268 CBE patients of Australian, British, German Italian, Spanish and Swedish origin and 1,354 ethnically matched controls and from 92 CBE case-parent trios from North America were analysed.

Quality of Life after Surgical Treatment for Esophageal Atresia: Long-Term Outcome of 154 Patients.

 The short- and long-term surgical results in patients with esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) have been described in depth from a physician's perspective. Contrarily, the perception and coping strategies of affected patients and their parents have rarely been reported. The aim of this study was to generate data on this matter.

Esophageal Atresia with or without Tracheoesophageal Fistula (EA/TEF): Association of Different EA/TEF Subtypes with Specific Co-occurring Congenital Anomalies and Implications for Diagnostic Workup.

Background:  Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) represents the most common developmental malformation of the upper digestive tract. It is classified into six subtypes according to the classification of Vogt, depending on anatomical variation of this malformation. Around 50% of the patients with EA/TEF present additional anomalies, which often influence, next to the EA/TEF subtype, the overall prognosis of EA/TEF newborns.

Evaluation of sexual function in females with exstrophy-epispadias-complex: A survey of the multicenter German CURE-Net.

Objective: Standardized knowledge about genital function in adult female individuals with exstrophy-epispadias complex (EEC) is scarce. The aim of this study was to investigate sexual function using the standardized Female Sexual Function Index (FSFI), and to assess the influence of bladder and vaginal reconstruction and the presence of incontinence on FSFI results.

Method: Sixty-one females (aged ≥18 years) recruited by the German multicenter network for congenital uro-rectal malformations (CURE-Net) were asked to complete the FSFI and a self-designed semi-structured questionnaire assessing comprehensive medical data, gynecological, and psychosocial items.